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Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation. (CANREN-AF)

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ClinicalTrials.gov Identifier: NCT03536806
Recruitment Status : Not yet recruiting
First Posted : May 25, 2018
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
Rafał Dąbrowski, Institute of Cardiology, Warsaw, Poland

Tracking Information
First Submitted Date  ICMJE May 12, 2018
First Posted Date  ICMJE May 25, 2018
Last Update Posted Date May 25, 2018
Estimated Study Start Date  ICMJE June 2018
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
Conversion of atrial fibrillation to sinus rhythm. [ Time Frame: Time Frame: 2 hours. ]
Conversion of atrial fibrillation to sinus rhythm confirmed in standard 12-lead ECG during observation period after first iv bolus.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
  • Time to conversion of atrial fibrillation to sinus rhythm. [ Time Frame: Time Frame: 2 hours. ]
    Time to conversion of atrial fibrillation to sinus rhythm in minutes since injection.
  • Atrial fibrillation recurrence within observation period. [ Time Frame: Time Frame: 2 hours. ]
    Atrial fibrillation recurrence within observation period.
  • Serious adverse reactions. [ Time Frame: Time Frame: 24 hours. ]
    Serious adverse reactions, which refer to every event requiring admission to a hospital or extended observation.
  • Safety outcome (exploratory analysis). [ Time Frame: Time Frame: 24 hours. ]
    hypotension < 90 mm Hg, cardiac conduction abnormalities, new arrhythmia occurrence, other
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation.
Official Title  ICMJE Clinical Efficacy of Potassium Canrenoate - Canrenone in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation and Elevated Blood Pressure - a Pilot Randomized Controlled Trial.
Brief Summary The purpose of this randomized, double blind, placebo-controlled, superiority clinical trial was to assess clinical efficacy of potassium canrenoate - canrenone in rapid conversion of atrial fibrillation to sinus rhythm.
Detailed Description

Canrenone is a specific antagonist of aldosterone. It is a competitive inhibitor of aldosterone receptors and inhibits the effects of aldosterone. Spironolactone is a prodrug which is active after its conversion into canrenone. By inhibiting the effects of aldosterone it increases aqueous and sodium diuresis and is classified as a diuretic. It decreases urinary elimination of potassium and increases urinary excretion of calcium. Canrenone is used for the treatment of primary or secondary hyperaldosteronism, edema and ascites of congestive heart failure and cirrhosis, and in the treatment of the arterial hypertension. Current evidence supports renin-angiotensin-alodsterone (RAAS) inhibition: angiotensin-converting-enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB) or, potentially, mineralocorticoid receptor antagonists (MRA) as an upstream therapy for atrial fibrillation (AF) management. It has been demonstrated that plasma aldosterone concentration may be increased in patients with AF episode, and it lowers after cardioversion. Only canrenone (potassium canrenoate) may be administered intravenously. Canrenone increases plasma level of potassium, lowers blood pressure and reduces preload at the same time.

To show superiority of canrenone over placebo a sample size of 80 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of canrenone 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description:
Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Atrial Fibrillation, Paroxysmal
Intervention  ICMJE
  • Drug: Saline 0.9%
    Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. BP will be measured before injection.
    Other Name: saline 0.9% in bolus of 10 cm3
  • Drug: Canrenone
    Patients assigned to canrenone group will be administered canrenone in bolus of 200 mg diluted to 10 cm3 within 2-3 minutes in one dose. Drug administration will be stopped in case of serious adverse event. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines.
    Other Name: canrenone in bolus of 200 mg diluted to 10 cm3
Study Arms  ICMJE
  • Placebo Comparator: Placebo Comparator: Placebo
    Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. After drug administration the patient will be observed for 2 hours after the last dose with exit ECG and BP measure taken at the end of observation. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines.
    Intervention: Drug: Saline 0.9%
  • Experimental: Experimental: canrenone
    Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. After administration of canrenone: dose 200 mg (1 ampule a 10 ml) within 2-3 minutes the patient will be observed for 2 hours after the dose with exit ECG and BP measure taken at the end of observation.
    Intervention: Drug: Canrenone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 23, 2018)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • written informed consent for enrolment
  • patients aged between 40 and 75 years
  • atrial fibrillation episode lasting for less than 48 hours, documented by the ECG
  • potassium plasma levels < 4.5 mmol/l
  • blood pressure > 120/80 mmHg
  • stable cardiopulmonary status (according to attending physician's assessment)
  • in case of left ventricle injury suspicion or unclear medical history of cardiac insufficiency, enrolment will be possible after echocardiographic examination

Exclusion Criteria:

  • no written informed consent for enrollment
  • allergy to canrenone
  • cardiac insufficiency or LVEF (left ventricular ejection fraction) < 40%
  • systolic BP < 120/80 mmHg
  • history of canrenone treatment in the 30 days before enrollment
  • average QRS rate > 160 p.m.
  • advanced hepatic or renal failure
  • history of acute coronary syndrome, CABG (coronary artery bypass grafting), TIA (transient ischemic attack) or stroke within the previous 30 days
  • pre-excitation syndrome (which has not been treated with accessory pathway ablation).
  • atrial fibrillation due to a valvular heart disease
  • atrial fibrillation episode resulting in myocardial ischemia (chest pain, ischemic changes in the ECG)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rafał Dąbrowski, MD, PhD +48 601250732 rdabrowski45@gmail.com
Contact: Paweł Syska, MD, PhD +48 604072667 psyskamd@gmail.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03536806
Other Study ID Numbers  ICMJE 2.62/VII/16
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Rafał Dąbrowski, Institute of Cardiology, Warsaw, Poland
Study Sponsor  ICMJE Institute of Cardiology, Warsaw, Poland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rafał Dąbrowski, MD, PhD Institute of Cardiology
Study Chair: Tomasz Hryniewiecki, MD, PhD Institute of Cardiology
PRS Account Institute of Cardiology, Warsaw, Poland
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP